title: Bioactive tumour necrosis factor alpha but not granulocyte-macrophage colony-stimulating factor correlates inversely with Langerhans's cell numbers in skin tumours.
abstract: Langerhans' cells (LCs) are thought to play an important role in presentation of tumour antigens for the induction of anti-tumour immunity. Epidermis overlying some transplanted murine skin tumours contains increased numbers of LCs; however, alterations in LC numbers are not related to tumour antigenicity or host immunity, suggesting that another factor(s), such as tumour-produced cytokines, influences LC density. It has been postulated that dendritic epidermal T cells (DETCs) play a role in immunosurveillance within the normal epidermis. Two cytokines which potentially alter LC numbers or function include granulocyte-macrophage colony-stimulating factor (GM-CSF) and tumour necrosis factor-alpha (TNF-alpha). GM-CSF maintains LC viability in culture, and there are reports that it can increase LC density. There is evidence that TNF-alpha induces LC to migrate from the epidermis. In the present study, LC densities in regressor and non-regressor murine skin tumours and overlying epidermis were enumerated, and bioactive GM-CSF and TNF-alpha present in the tumours were measured. We found significantly increased epidermal LC numbers above non-regressor, but not regressor, tumours. DETC numbers were significantly increased above some tumours. Although all tumour types produced TNF-alpha, the regressors, which did not increase LC numbers, produced the most TNF-alpha. In contrast, tumour production of GM-CSF did not correlate with any pattern of alteration of LC density or tumour growth. Tumour production of neither cytokine nor tumour growth correlated with DETC numbers overlying tumours. Our results suggest that TNF-alpha may be associated with skin tumour regression and may prevent LC accumulation by tumours.
authors.affiliation: Department of Medicine (Dermatology), University of Sydney at Royal Prince Alfred Hospital, Camperdown, NSW, Australia.
authors.forename: D M
authors.initials: DM
authors.lastname: Rubel
authors.forename: R S
authors.initials: RS
authors.lastname: Barnetson
authors.forename: G M
authors.initials: GM
authors.lastname: Halliday
mesh_terms: D000818:Animals; D002452:Cell Count; D003713:Dendritic Cells / Q000502:physiology; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000502:physiology*; D007801:Langerhans Cells / Q000502:physiology*; D051379:Mice; D008809:Mice, Inbred C3H; D009368:Neoplasm Transplantation; D012878:Skin Neoplasms / Q000276:immunology*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
chemical_list: D014409:Tumor Necrosis Factor-alpha; D016178:Granulocyte-Macrophage Colony-Stimulating Factor